In general, our purpose is to expand continuing, and start new, projects to study the factors responsible for abnormal responses of humans to drugs. We will look at environmental factors (exposure to environmental pollutants, other drugs, etc.) and factors inherent to the patient (disease states or pre-existing pathological conditions, hormonal variations, immunologic, genetic, etc). These studies will be performed at the clinical level, utilizing animals to help explain the phenomena seen in humans, as well as to suggest possible approaches for similar studies in humans. In addition to utilizing existing methods, efforts will be directed toward developing methods to quantitate drug action, absorption, distribution and metabolism in the intact human.